October 2005
ANATOMIC PATHOLOGY
Breast
Pathology Practice: Most Common Problems In A Consultation Service
Putti T C, Pinder S E,
Elston C W et al
Considerable progress has been made in understanding breast lesions utilizing molecular methods, but conventional morphology, simple immunohistochemical stains and common sense still prevail in diagnosing the vast majority of breast disease. The focus of this review is to identify the most common breast lesions sent to our consultation practice, and to reiterate salient diagnostic features, differential diagnoses and common pitfalls in identifying these lesions. Separation of epithelial proliferative lesions and differentiation between usual epithelial hyperplasia (UEH) and atypical ductal hyperplasia (ADH) are the most common problems encountered in our Consultation practice. Differentiation between UEH and ADH is based on the assumption that ADH is a clonal process, recognized by a uniform phenotype and more recently described immunohistochemical markers such as differential cytokeratin and also hormone receptor expression. Difficulty in subtyping invasive carcinomas and exclusion of in situ and/or invasive carcinoma in a sclerosing lesion is also commonly noted. Finally, problems in distinguishing various papillary and fibroepithelial lesions are also encountered. The use of common immunohistochemical stains such as various cytokeratin and myoepithelial markers, E-cadherin and hormone receptors is helpful in solving most of these diagnostic dilemmas.
Histopathology,
Volume 47 Issue 5 Page 445 - November 2005
P53 And C-Kit
(Cd117) Protein Expression As Prognostic Indicators In Breast Phyllodes Tumors:
A Tissue Microarray Study
Puay-Hoon Tan, Thiyagarajan
Jayabaskar, George Yip Bay et al
Breast
phyllodes tumors are fibroepithelial neoplasms whose clinical behavior is
difficult to predict on histology. There is relatively scant data on the role
of biological markers. In this study, authors determined if p53 and CD117
(c-kit) protein expression was predictive of behavior in a series of 335
phyllodes tumors diagnosed at the
Modern Pathology advance online publication
A
Tumor-Like Lymphocytis Mastitis
[Article in French]
Giusiano S, Andrac-Meyer L,
Meunier-Carpentier S, Xerri L, Boubli L et al
A
44-year-old woman presenting with an inflammatory and palpable firm breast lump
underwent surgical excision. Intraoperative frozen section analysis showed an
extensive lesion consisting of ducts with intraluminal "necrosis". In
addition, a very dense stromal inflammation was observed around these ducts,
suggesting an invasive ductal carcinoma with predominant intraductal
proliferation. However, on paraffin sections, epithelial cells close to the
lymphocytic infiltrate were rare, subatrophic, without any neoplastic feature.
The density and architecture of the lymphocytic infiltrate mimicked a breast
lymphoma. However, immunochemistry and molecular biology investigation favored
the diagnosis of a tumor-like lymphocytic mastitis. Although extremely rare,
this particular form of lymphocytic mastitis, a diagnostic pitfall particulary
during peroperative examination, should be recognized by pathologists.
Rare expression
of T-cell markers in classical Hodgkin's lymphoma
Alexandar Tzankov, Caroline
Bourgau, Alexandra Kaiser et al
Hodgkin's and Reed-Sternberg cells of classical
Hodgkin's lymphoma are primarily of B-cell origin, although there are instances
of T-cell antigen expression suggesting T-cell origin.Authors comprehensively
analyzed expression of various T-cell antigens in 259 classical Hodgkin's
lymphoma cases using the tissue microarray technique. Expression of the T-cell
antigens CD2, CD3, CD4, CD5, CD7 and CD8 was assessed by immunohistochemistry.
Hodgkin's and Reed-Sternberg cells of T-cell
marker-positive cases were microdissected and analyzed by a multiplex
polymerase chain reaction for clonal immunoglobulin heavy chain- and T-cell
receptor 
gene rearrangements. In all, 12
cases (5%) expressed at least one T-cell marker in the following order: CD2 in
11 cases, CD4 in five, CD3 in two, and CD5 and CD8 in one case each; there were
no CD7-positive cases, and five cases (2%) expressed more than one T-cell
antigen. In positive cases, a mean fraction of 40% of the Hodgkin's and Reed-Sternberg cells (range 20-100%) expressed the analyzed T-cell
markers. Two cases (<1%) evidenced clonal T-cell receptor g gene rearrangement. Phenotypic
expression of T-cell antigens in Hodgkin's and Reed-Sternberg cells of classical
Hodgkin's lymphoma is rare (5%), while genotypically, less than 1% of classical
Hodgkin's lymphomas are of possible T-cell origin. Therefore, T-cell antigen
expression on Hodgkin's and Reed-Sternberg cells is aberrant in the
majority of cases and only infrequently classical Hodgkin's lymphomas are of
T-cell origin.
Traverse-Glehen A, Pittaluga S, Gaulard P,
Sorbara L et al
In
recent years, overlap in biologic and morphologic features has been identified
between classic Hodgkin lymphoma (cHL) and B-cell non-Hodgkin lymphoma.
Nevertheless, the therapeutic approaches for these diseases remain different.
Authors undertook a study of "mediastinal gray zone lymphomas"
(MGZL), with features transitional between cHL nodular sclerosis (NS) and
primary mediastinal large B-cell lymphoma (MLBCL) to better understand the
morphologic and immunophenotypic spectrum of such cases. Twenty-one MGZL cases
were identified over a 20-year period. Authors also studied 6 cases of
composite or synchronous lymphoma with two distinct components at the same time
(cHL-NS and MLBCL) and 9 sequential cases with MLBCL and cHL-NS at different
times. All patients had a large mediastinal mass. Immunohistochemical studies
focused on markers known to discriminate between cHL and MLBCL, including
B-cell transcription factors. VJ-PCR was performed in 8 cases to look at
clonality of the immunoglobulin heavy chain gene (IgH). Of the gray zone cases,
11 had morphology reminiscent of cHL-NS, but with unusual features, including a
large number of mononuclear variants, diminished inflammatory background,
absence of classic Hodgkin phenotype, and strong CD20 expression (11 of 11).
Ten cases had morphology of MLBCL, but with admixed Hodgkin/Reed-Sternberg and
lacunar cells, absent (3 of 10) or weak (7 of 10) CD20 expression, and
positivity for CD15 in 7 cases. B-cell transcription factor expression in the
gray zone cases more closely resembled MLBCL than cHL with expression of Pax5,
Oct2, and BOB.1 in all but 1 case studied (14 of 15). MAL staining was found in
7 of 10 MGZL, and in at least one component of 6 of 7 evaluable composite or
sequential MLBCL/cHL cases. Two cases of sequential lymphoma showed
rearrangements of the IgH gene of identical size: one in which MLBCL was the
first diagnosis and one in which MLBCL was diagnosed at relapse, indicating
clonal identity for the two components of cHL and MLBCL. There is accumulating
evidence that MLBCL and cHL are related entities. Further support for a
relationship between MLBCL and cHL-NS is provided by composite and metachronous
lymphomas in the same patient, as well as the existence of MGZL with
transitional morphology and phenotype.
Am J Surg Pathol. 2005 Nov;29(11):1411-1421.
Lymphoplasmacytic
Lymphoma/Waldenstrom Macroglobulinemia: An Evolving Concept
Lin P,
Medeiros LJ.
The concept of Waldenstrom macroglobulinemia has
evolved from the original description of a clinical syndrome to its more recent
designation as a distinct clinicopathologic entity, that is, lymphoplasmacytic
lymphoma/Waldenstrom macroglobulinemia (LPL/WM), in the World Health
Organization (WHO) classification and by the participants of consensus meetings
on WM. The diagnosis of LPL/WM, however, remains a challenge in daily practice.
Distinguishing LPL/WM from other B-cell lymphomas, especially marginal zone
B-cell lymphomas, which share overlapping morphologic features, is difficult.
The traditional practice of separating LPL/WM from other lymphomas by an
arbitrary level of serum IgM is no longer considered valid. The characteristic
immunophenotype described for LPL/WM by the WHO classification, that is,
CD5CD10CD23, is observed in 60-80% of neoplasms, but variations from this
pattern of antigen expression are common, with CD23 being detected in up to 40%
of cases. Lack of a distinct molecular genetic hallmark complicates the
distinction of LPL/WM from other B-cell lymphomas. Although the t(9;14) is
stated to be present in 50% of cases in the WHO classification, translocations
involving the Ig heavy chain including the t(9;14) are actually rare in LPL/WM.
Deletion of 6q21-q23, a nonspecific finding, is the most common aberration
reported in 40-70% of patients. At the molecular level, the neoplastic clone in
most cases has undergone Ig variable gene mutation, but not isotype switching,
and the clone retains the capability of plasmacytic differentiation. Currently,
the diagnosis of LPL/WM can only be established by incorporating clinical and
pathologic findings and excluding alternative diagnoses. In some cases, in
authors opinion, distinguishing LPL/WM from marginal zone B-cell lymphomas
seems arbitrary using currently recommended criteria.
Adv Anat Pathol. 2005 Sep;12(5):246-55.
Immunostain CD138
May Improve Detection Rate of Chronic Endometritis
Oct. 10, 2005 (Seattle) The use of CD138
immunostaining may improve the detection rate of chronic endometritis while
reducing the pathologist's lab time, according to research presented here at
the annual meeting of the American Society for Clinical Pathology.
Chronic endometritis, an inflammation of the uterine lining, is believed to be
caused by various infectious organisms. Pathologists typically diagnose the
condition by laboriously scanning slide specimens for the presence of plasma
cells, which are associated with chronic inflammation.
"Finding plasma cells is difficult," lead author Sharon Fuentes, MD,
a pathology resident at the
Researchers used an immunostain for CD138, a plasma cellsurface glycoprotein, to
detect the presence of plasma cells. The researchers reviewed endometrial
samples taken from 107 women aged 20 to 35 years who had been diagnosed with
either chronic endometritis or abnormal bleeding with otherwise normal
endometrial linings that were either proliferative, secretory, shedding, or
anovulatory.
The samples were stained for CD138 as well as tryptase, an enzyme that detects
mast cells, which may resemble plasma cells and lead to false diagnoses of
chronic endometritis. Two separate pathologists who were blinded to the
original diagnosis reviewed the slides.
Of the 28 cases of chronic endometritis, just 18 samples were positive for
CD138 and negative for tryptase, indicating an accurate diagnosis. However, Dr.
Fuentes said, 10 samples were CD138-negative but tryptase-positive, indicating
that mast cells had "fooled" pathologists into returning a 35%
false-positive rate.
Similarly, 32 (40%) of the 79 "benign" samples were determined to be
false-negatives, with positive results from the CD138 immunostain and negative
results from tryptase.
The high rate of false-negatives could leave patients with unexplained
excessive bleeding, leading to a hysterectomy that could be unwarranted, Dr.
Fuentes noted. Eight percent of her samples were from hysterectomies. The use
of the immunostain could improve the accuracy of diagnoses, she added.
"Those false-negatives should have been picked up," Dr. Fuentes told
Medscape. "With this technique, we could help them, treat their
endometritis with antibiotics, if clinically indicated. Doctors should consider
using this stain to prevent women from undergoing unnecessary
hysterectomies."
Another benefit to the immunostain is the time-saving aspect. The pathologists
spent an average of three minutes inspecting the traditional hematoxylin and
eosin slides compared with 15 seconds reviewing the immunostained slides. The
total time spent analyzing the samples dropped from 5.35 hours to 53.6 minutes
using the immunostain, or a 30-fold reduction. "It's a time benefit to the
pathologist," Dr. Fuentes said.
While immunohistochemistry is more costly, Dr. Fuentes pointed out, the
technique could reduce patholgists time searching for plasma cells, as well as
prevent the cost of unnecessary surgery for a treatable condition.
ASCP 2005 Annual Meeting: Abstract 72. Presented
Reviewed by Gary D. Vogin, MD
CLINICAL PATHOLOGY
Evaluation
of Taenia solium and Taenia crassiceps cysticercal antigens for the
serodiagnosis of neurocysticercosis
Arruda GC, da Silva AD, Quagliato EM et al
Authors evaluated the usefulness of seven
cysticercal antigen extracts, four from Taenia solium cysticerci (whole
parasite-TsoW, membrane-TsoMe, vesicular fluid-TsoVF and scolex-TsoSc) and
three from T. crassiceps cysticerci (whole parasite-TcraW, membrane-TcraMe and
vesicular fluid-TcraVF), for serodiagnosis of neurocysticercosis with an
enzyme-linked immunosorbent assay (ELISA). Cysticercus-specific IgG were
screened in serum samples from 23 patients with neurocysticercosis, 32 patients
with other infections and 48 healthy persons. The best results were obtained
with the TsoVF-ELISA (91.3% sensitivity; 96.2% specificity) and TcraVF-ELISA
(91.3% sensitivity; 95% specificity). The ELISA done with whole parasite and
membrane extracts from cysts of T. solium and T. crassiceps and the scolex
extract from T. solium cysts showed a low performance in terms of sensitivity,
ranging from 47.8% to 73.9%. None of the antigen preparations from T. solium
and T. crassiceps cysticerci used in this study showed outstanding performance
for the serodiagnosis of neurocysticercosis. However, considering the results
obtained with the seven antigen preparations, vesicular fluid from T. solium
and T. crassiceps cysticerci may be useful for detecting specific antibodies in
sera from patients with neurocysticercosis.
High Normal Fasting Plasma
Glucose Points To Diabetes
NEW YORK (Reuters Health) - Having a higher fasting plasma glucose level within the normoglycemic range is an independent risk factor for type 2 diabetes among young men, Israeli researchers report in the October 6th issue of the New England Journal of Medicine.
Dr. Amir Tirosh, from
In multivariate analysis that adjusted for age, body mass index (BMI), triglyceride levels, physical activity, family history, and smoking status, subjects in the top three quintiles of fasting plasma glucose levels had significantly higher risk of diabetes compared with the lowest quintile.
Among men who were obese (BMI greater than 30) and in the highest quintile of fasting glucose, the hazard ratio for diabetes was 8.29 compared with normal weight men in the lowest quintile of plasma glucose. Similarly, among men with elevated serum triglyceride levels (beyond 150 mg/dL) and in the highest quintile of fasting glucose, the hazard ratio was 8.23.
"The identification of a high-normal fasting plasma glucose level as a risk factor for type 2 diabetes may help to identify young, healthy men for whom preventive interventions might be considered," Dr. Tirosh's team observes. They suggest that lifestyle modifications, glucose-lowering medications, and the anti-obesity drug orlistat could be used to delay the onset of diabetes in these patients.
Writing in a related editorial, Dr. Ronald A.
Arky from
N Engl J Med 2005;353:1454-1462,1511-1513.
Diabetes Reversed
A single transplant of living-donor islet cells from the distal pancreas of a healthy mother has successfully reversed brittle diabetes in her 27-year-old daughter. In January 2005, the donor mother underwent a distal pancreatectomy. More than 400 000 islet equivalents were isolated from the pancreatic tail and immediately transplanted into the recipient daughters liver via access to the percutaneous portal vein under local anaesthesia. The daughter became insulin-independent from the 22nd day after transplantation. Because she did not have autoimmune type 1 diabetes, the transplanted islets did not need protection against autoimmune disease. The mother had no complications.
The procedure took place in
Lancet 2005; 365: 1642-1644